Obstructive Sleep ApneaCytokine OSANCT02325687
A Pilot Study of Biomarkers in Obstructive Sleep Apnea
A study testing Lumbar Puncture (Standard-of-Care) in people with Obstructive Sleep Apnea, run by Hospital for Special Surgery, New York at 1 site in United States.
Trial summary
Obstructive sleep apnea (OSA) is common and is a risk factor for postoperative complications, including respiratory and cardiac events and delirium. Despite this risk, however, there are currently no accepted biomarkers that can predict poor outcomes, making it unclear to see which patients will have complications… Read more about this study
- Who is it for?
- Ages 50 to 84 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Lumbar Puncture (Standard-of-Care)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Nov 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients between the ages of 50 and 84
- Treated and Untreated OSA Patients: Known OSA, diagnosed by polysomnography
- Treated OSA Patients: Known CPAP prescription, dose used nightly, and compliance status
- Controls: No suspicion for OSA, based on STOP-BANG screening score (<3)
- Any patient presenting for knee replacement surgery with prior consent for spinal or combined spinal-epidural anesthesia
Who cannot join
- Presence of dementia
- Presence of cognitive disease
- Presence of depression, anxiety, or other mood disorder(s)
- Recent oral steroid therapy (within prior 6 months)
- Requirement of stress-dose steroids pre-operatively
- Autoimmune disease
Show all 14Show fewer
- Neurologic disease
- Controls: Suspected OSA, either disclosed by patient, or by clinical suspicion based on STOP-BANG questionnaire (score ≥ 3)
- Chronic renal disease
- Chronic liver disease
- Traumatic spinal or spinal-epidural placement (i.e., blood-contaminated CSF)
- Alcohol abuse - defined as being diagnosed with alcohol abuse or consuming more than 2 drinks per night, on average
- Use of NSAIDs within 7 days prior to surgery
- Chronic benzodiazepine use (for more than one month)
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital for Special Surgery
New York, New York, 10021
About this study
Official title: A Pilot Study of Biomarkers in Obstructive Sleep Apnea (OSA): Is There a Correlation Between Cerebrospinal Fluid and Serum Markers of Inflammation in OSA?
Obstructive sleep apnea (OSA) is common and is a risk factor for postoperative complications, including respiratory and cardiac events and delirium. Despite this risk, however, there are currently no accepted biomarkers that can predict poor outcomes, making it unclear to see which patients will have complications after surgery, and who might need prolonged monitoring or an extended hospital stay. An improved understanding of the pathophysiology of OSA is required to identify potential biomarkers for outcomes after surgery, as well as to develop new treatments. The aim of this pilot study is to identify serum and cerebrospinal (CSF) biomarkers associated with obstructive sleep apnea (OSA). The presence of cytokines and neurotrophins will be determined and quantified in both patients with OSA and in controls. The CSF samples will additionally be analyzed by proteomic methods to identify potential biomarkers with significantly different levels present in patients with and without OSA. The working hypothesis is that OSA patients who are non-CPAP-compliant will have higher levels of circulating cytokines and lower levels of circulating neurotrophins in serum and CSF, compared to patients who are CPAP-compliant and/or controls.
Read the detailed description
It is being increasingly understood that OSA represents an inflammatory state, with multiple studies showing increased levels of circulating cytokines, possibly providing the link between OSA and cardiovascular/pulmonary morbidity. In support of this, use of CPAP therapy is associated with a reduction in the levels of circulating cytokines in patients with OSA. Despite these data, to our knowledge, there are no studies that specifically examine the association between the presence of cytokines and surgical complications. The present investigation may be helpful for future studies looking at this relationship.Inflammation has recently been emphasized as a component of the CNS manifestations of OSA as well, including generalized cognitive deficits and post-operative delirium. It is possible that intermittent hypoxia leads to CNS inflammation/activation of microglia (as has been shown in in vitro studies), which, together with blood-brain barrier (BBB) breakdown (recently shown to be involved in OSA), results in elevated circulating peripheral levels of cytokines. Alternatively (or additionally), there could be direct peripheral activation of systemic macrophages as a consequence of sleep deprivation and the cortisol/stress response to this condition. In any event, to date, there are no studies exploring the presence or levels of cytokines in the CSF of patients with OSA. In addition to the release of inflammatory cytokines, activation of microglia causes the release of neuroprotective neurotrophins. Alterations in levels of several neurotrophins have been implicated in multiple CNS diseases. For example, in Parkinson's disease, there is a known elevation in cytokines with reduced circulating levels of CSF neurotrophins (BDNF and NGF) and this balance has been posited to underlie some of the symptoms and progression of the disease. BDNF has recently been shown to protect against the development of Alzheimer's disease and dementia, as well as to increase with caloric restriction and physical activity.
Considering OSA is associated with obesity, it is possible that low BDNF may (at least in part) mediate some of the cognitive deficits seen in OSA. Additionally, low BDNF is associated with postoperative delirium in clinical studies. Currently, the role of neurotrophins in OSA remains underinvestigated. Of all the known neurotrophins, only BDNF has been studied in OSA patients, and the results are conflicting, with some studies suggesting reduced levels of serum BDNF and others showing no differences compared to control patients. This may in part be due to the detection methods employed or small sample sizes, and to date, no one has investigated CSF levels of neurotrophins in this patient population. Here we hypothesize that the detrimental effects of circulating cytokines in OSA may be balanced in some patients by beneficial effects exerted by neurotrophins, and that this differential balance may represent: 1) a tool for identifying which patients are at risk for post-operative complications in future studies, i.e., a useful biomarker for stratifying operative risk; 2) a new understanding of the pathophysiology of OSA; and 3) a role for neuroprotective strategies in the management of OSA.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Lumbar Puncture (Standard-of-Care)
- Keywords
- Obstructive Sleep Apnea, Arthroplasty, Replacement, Knee, Cerebrospinal Fluid, Inflammation, TNF-alpha, Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Cytokines, Neurotrophins, BDNF, Beta-NGF, Proteomic Analysis
- Medical subject headings
- Sleep Apnea, Obstructive, Inflammation, Pain Insensitivity, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lumbar Puncture (Standard-of-Care)Procedure or surgery
All study patients will have previously consented to undergo either spinal or spinal-epidural anesthesia. Patients will undergo their planned spinal or combined spinal-epidural placement in the OR. At the time of confirmation of placement of the spinal needle (positive CSF flow), 5 mL CSF will be collected and stored. CSF will be drawn using a standard 25g or 27g needle commonly used for anesthesia. The volume of CSF removed will be replaced with 4 cc local anesthetic (1.5% mepivacaine for spinal anesthesia).
| Study group | Role | What they receive |
|---|---|---|
| Treated OSA (CPAP-compliant) | Experimental | Treated OSA patients will have previously been diagnosed with OSA, and are currently CPAP-compliant. CPAP compliance is defined by daily use of a CPAP machine for at least 4 hours. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient.
Intervention: Lumbar Puncture (Standard-of-Care) Receives: Procedure: Lumbar Puncture (Standard-of-Care) |
| Untreated OSA (non-CPAP-compliant) | Experimental | Patients in the untreated OSA group will have previously been diagnosed with OSA, but for some reason do not use a CPAP machine every night. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient.
Intervention: Lumbar Puncture (Standard-of-Care) Receives: Procedure: Lumbar Puncture (Standard-of-Care) |
| Control (No suspicion of OSA) | Experimental | Patients in the control group will not have previously been diagnosed with OSA, and are currently not at high risk. We will determine overall risk for OSA using the STOP-BANG questionnaire. Patients with a STOP-BANG score <3 are considered to have minimal risk for OSA and will be included in the control group.
Intervention: Lumbar Puncture (Standard-of-Care) Receives: Procedure: Lumbar Puncture (Standard-of-Care) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum IL-6 (Interleukin 6) Levels
The primary outcome, the levels of cytokine IL-6 in serum of OSA-treated, OSA-untreated and control patients presenting for knee replacement surgery with planned spinal or combined spinal-epidural anesthesia.
Measured: Intraoperatively - Pre-Incision
Secondary outcomes (6)
Serum and CSF (Cerebrospinal Fluid) Levels of the Cytokines TNF-alpha (Tumor Necrosis Factor) , IL-6, IL-8, IL-10 (Interleukin)
Biological samples were collected, but not analyzed for the presence and levels of particular cytokines (TNF-alpha, IL-6, IL-8, IL-10) and neurotrophins (BDNF(brain-derived neurotrophic factor), β-NGF (nerve growth factor)) due to the integrity of the samples.
Measured: Intraoperatively - Pre-Incision
Serum and CSF Levels of the Neurotrophins BDNF, IFN-gamma (Interferon Gamma)
CSF (cerebrospinal fluid) was planned to be screened for the differential expression of proteins.The samples have been collected, but the assays have not been performed due to the integrity of the samples.
Measured: Intraoperatively - Pre-Incision
Number of Participants With Respiratory, Cardiac, and/or CNS (Central Nervous System) Complications
We will look at the incidence of respiratory complications (hypoxia; need for respiratory intervention), cardiac complications (MI/ACS or arrhythmias) and CNS (central nervous system) complications (delirium, TIA or CVA). Parameters will be scored for presence or absence over the entire length of stay.
Measured: Throughout hospital stay, or an average of 1 week.
Incidence of Intraoperative Obstructive Respiratory Events
Incidences of intraoperative obstructive respiratory events will be collected perioperatively in the operating room by the anesthesiologist
Measured: Throughout hospital stay, or an average of 1 week.
Levels of Blood Oxygen Saturation
Levels of blood oxygen saturation will be measured via arterial blood gas levels. These will be drawn as standard-of-care.
Measured: Throughout stay in the recovery unit, or an average of 1-2 days.
Length of Stay in the Recovery Unit
Levels of blood oxygen saturation throughout the length of stay in the recovery unit will be measured via arterial blood gas levels, found in the patient's electronic medical record
Measured: Throughout stay in the recovery unit, or an average of 1-2 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Hospital for Special Surgery, New YorkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital for Special Surgery, New York
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kethy M Jules-Elysee, MD, Principal investigator, Hospital for Special Surgery, New York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325687
- Sponsor's protocol ID
- 2014-100
- Acronym
- Cytokine OSA
- Status last verified
- Apr 2020
- First submitted
- 10 Dec 2014
- Last updated
- 21 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):268-86. doi: 10.1097/ALN.0000000000000053. No abstract available.
PubMed 24346178Aisen PS. Serum brain-derived neurotrophic factor and the risk for dementia. JAMA. 2014 Apr 23-30;311(16):1684-5. doi: 10.1001/jama.2014.3120. No abstract available.
PubMed 24756518Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, Naseem J, Asif A, Bawaadam H. Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013 Mar 22;10:13. doi: 10.1186/1476-9255-10-13. eCollection 2013.
PubMed 23518041Flink BJ, Rivelli SK, Cox EA, White WD, Falcone G, Vail TP, Young CC, Bolognesi MP, Krystal AD, Trzepacz PT, Moon RE, Kwatra MM. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology. 2012 Apr;116(4):788-96. doi: 10.1097/ALN.0b013e31824b94fc.
PubMed 22337162Grandi C, Tomasi CD, Fernandes K, Stertz L, Kapczinski F, Quevedo J, Dal-Pizzol F, Ritter C. Brain-derived neurotrophic factor and neuron-specific enolase, but not S100beta, levels are associated to the occurrence of delirium in intensive care unit patients. J Crit Care. 2011 Apr;26(2):133-7. doi: 10.1016/j.jcrc.2010.10.006. Epub 2010 Nov 23.
PubMed 21106342Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest. 2012 Jun;141(6):1601-1610. doi: 10.1378/chest.11-2214.
PubMed 22670023Lim DC, Pack AI. Obstructive sleep apnea and cognitive impairment: addressing the blood-brain barrier. Sleep Med Rev. 2014 Feb;18(1):35-48. doi: 10.1016/j.smrv.2012.12.003. Epub 2013 Mar 28.
PubMed 23541562Nakajima K, Kohsaka S. Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord. 2004 Mar;4(1):65-84. doi: 10.2174/1568006043481284.
PubMed 15032653Nadeem R, Molnar J, Madbouly EM, Nida M, Aggarwal S, Sajid H, Naseem J, Loomba R. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med. 2013 Oct 15;9(10):1003-12. doi: 10.5664/jcsm.3070.
PubMed 24127144Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl. 2000;(60):277-90. doi: 10.1007/978-3-7091-6301-6_19.
PubMed 11205147Panaree B, Chantana M, Wasana S, Chairat N. Effects of obstructive sleep apnea on serum brain-derived neurotrophic factor protein, cortisol, and lipid levels. Sleep Breath. 2011 Dec;15(4):649-56. doi: 10.1007/s11325-010-0415-7. Epub 2010 Sep 24.
PubMed 20865453Yang Q, Wang Y, Feng J, Cao J, Chen B. Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia. Neuropsychiatr Dis Treat. 2013;9:1077-86. doi: 10.2147/NDT.S49868. Epub 2013 Aug 5.
PubMed 23950649Wang WH, He GP, Xiao XP, Gu C, Chen HY. Relationship between brain-derived neurotrophic factor and cognitive function of obstructive sleep apnea/hypopnea syndrome patients. Asian Pac J Trop Med. 2012 Nov;5(11):906-10. doi: 10.1016/S1995-7645(12)60169-2.
PubMed 23146807
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Biomarkers in Obstructive Sleep Apnea (OSA): Is There a Correlation Between Cerebrospinal Fluid and Serum Markers of Inflammation in OSA?
- ClinicalTrials.gov ID
- NCT02325687
- Acronym / sponsor ID
- Cytokine OSA / 2014-100
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive Sleep Apnea, Arthroplasty, Replacement, Knee, Cerebrospinal Fluid, Inflammation, TNF-alpha, Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Hospital for Special Surgery, New YorkUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Posted 21 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obstructive sleep apnea (OSA) is common and is a risk factor for postoperative complications, including respiratory and cardiac events and delirium. Despite this risk, however, there are currently no accepted biomarkers that can predict poor outcomes, making it unclear to see which patients will have complications after surgery, and who might need prolonged monitoring or an extended hospital stay. An improved understanding of the pathophysiology of OSA is required to identify potential biomarkers for outcomes after surgery, as well as to develop new treatments. The aim of this pilot study is to identify serum and cerebrospinal (CSF) biomarkers associated with obstructive sleep apnea (OSA). The presence of cytokines and neurotrophins will be determined and quantified in both patients with OSA and in controls. The CSF samples will additionally be analyzed by proteomic methods to identify potential biomarkers with significantly different levels present in patients with and without OSA. The working hypothesis is that OSA patients who are non-CPAP-compliant will have higher levels of circulating cytokines and lower levels of circulating neurotrophins in serum and CSF, compared to patients who are CPAP-compliant and/or controls.
Detailed description
It is being increasingly understood that OSA represents an inflammatory state, with multiple studies showing increased levels of circulating cytokines, possibly providing the link between OSA and cardiovascular/pulmonary morbidity. In support of this, use of CPAP therapy is associated with a reduction in the levels of circulating cytokines in patients with OSA. Despite these data, to our knowledge, there are no studies that specifically examine the association between the presence of cytokines and surgical complications. The present investigation may be helpful for future studies looking at this relationship.Inflammation has recently been emphasized as a component of the CNS manifestations of OSA as well, including generalized cognitive deficits and post-operative delirium. It is possible that intermittent hypoxia leads to CNS inflammation/activation of microglia (as has been shown in in vitro studies), which, together with blood-brain barrier (BBB) breakdown (recently shown to be involved in OSA), results in elevated circulating peripheral levels of cytokines. Alternatively (or additionally), there could be direct peripheral activation of systemic macrophages as a consequence of sleep deprivation and the cortisol/stress response to this condition. In any event, to date, there are no studies exploring the presence or levels of cytokines in the CSF of patients with OSA. In addition to the release of inflammatory cytokines, activation of microglia causes the release of neuroprotective neurotrophins. Alterations in levels of several neurotrophins have been implicated in multiple CNS diseases. For example, in Parkinson's disease, there is a known elevation in cytokines with reduced circulating levels of CSF neurotrophins (BDNF and NGF) and this balance has been posited to underlie some of the symptoms and progression of the disease. BDNF has recently been shown to protect against the development of Alzheimer's disease and dementia, as well as to increase with caloric restriction and physical activity.
Considering OSA is associated with obesity, it is possible that low BDNF may (at least in part) mediate some of the cognitive deficits seen in OSA. Additionally, low BDNF is associated with postoperative delirium in clinical studies. Currently, the role of neurotrophins in OSA remains underinvestigated. Of all the known neurotrophins, only BDNF has been studied in OSA patients, and the results are conflicting, with some studies suggesting reduced levels of serum BDNF and others showing no differences compared to control patients. This may in part be due to the detection methods employed or small sample sizes, and to date, no one has investigated CSF levels of neurotrophins in this patient population. Here we hypothesize that the detrimental effects of circulating cytokines in OSA may be balanced in some patients by beneficial effects exerted by neurotrophins, and that this differential balance may represent: 1) a tool for identifying which patients are at risk for post-operative complications in future studies, i.e., a useful biomarker for stratifying operative risk; 2) a new understanding of the pathophysiology of OSA; and 3) a role for neuroprotective strategies in the management of OSA.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treated OSA (CPAP-compliant) | Experimental | Procedure: Lumbar Puncture (Standard-of-Care)Treated OSA patients will have previously been diagnosed with OSA, and are currently CPAP-compliant. CPAP compliance is defined by daily use of a CPAP machine for at least 4 hours. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient. Intervention: Lumbar Puncture (Standard-of-Care) |
| Untreated OSA (non-CPAP-compliant) | Experimental | Procedure: Lumbar Puncture (Standard-of-Care)Patients in the untreated OSA group will have previously been diagnosed with OSA, but for some reason do not use a CPAP machine every night. We will determine if patients are CPAP-compliant by looking at their medical records and pre-operative assessments, as well as directly verifying compliance with the patient. Intervention: Lumbar Puncture (Standard-of-Care) |
| Control (No suspicion of OSA) | Experimental | Procedure: Lumbar Puncture (Standard-of-Care)Patients in the control group will not have previously been diagnosed with OSA, and are currently not at high risk. We will determine overall risk for OSA using the STOP-BANG questionnaire. Patients with a STOP-BANG score <3 are considered to have minimal risk for OSA and will be included in the control group. Intervention: Lumbar Puncture (Standard-of-Care) |
Who may qualify
- Ages
- 50 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients between the ages of 50 and 84
- Treated and Untreated OSA Patients: Known OSA, diagnosed by polysomnography
- Treated OSA Patients: Known CPAP prescription, dose used nightly, and compliance status
- Controls: No suspicion for OSA, based on STOP-BANG screening score (<3)
- Any patient presenting for knee replacement surgery with prior consent for spinal or combined spinal-epidural anesthesia
Key exclusion criteria (14 listed)
- Presence of dementia
- Presence of cognitive disease
- Presence of depression, anxiety, or other mood disorder(s)
- Recent oral steroid therapy (within prior 6 months)
- Requirement of stress-dose steroids pre-operatively
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lumbar Puncture (Standard-of-Care)All study patients will have previously consented to undergo either spinal or spinal-epidural anesthesia. Patients will undergo their planned spinal or combined spinal-epidural placement in the OR. At the time of confirmation of placement of the spinal needle (positive CSF flow), 5 mL CSF will be collected and stored. CSF will be drawn using a standard 25g or 27g needle commonly used for anesthesia. The volume of CSF removed will be replaced with 4 cc local anesthetic (1.5% mepivacaine for spinal anesthesia). | Procedure or surgery | Control (No suspicion of OSA), Treated OSA (CPAP-compliant), Untreated OSA (non-CPAP-compliant) |
Primary outcome
Serum IL-6 (Interleukin 6) Levels
Time frame: Intraoperatively - Pre-Incision
The primary outcome, the levels of cytokine IL-6 in serum of OSA-treated, OSA-untreated and control patients presenting for knee replacement surgery with planned spinal or combined spinal-epidural anesthesia.
6 secondary outcomes
Serum and CSF (Cerebrospinal Fluid) Levels of the Cytokines TNF-alpha (Tumor Necrosis Factor) , IL-6, IL-8, IL-10 (Interleukin)
Time frame: Intraoperatively - Pre-Incision
Serum and CSF Levels of the Neurotrophins BDNF, IFN-gamma (Interferon Gamma)
Time frame: Intraoperatively - Pre-Incision
Number of Participants With Respiratory, Cardiac, and/or CNS (Central Nervous System) Complications
Time frame: Throughout hospital stay, or an average of 1 week.
Incidence of Intraoperative Obstructive Respiratory Events
Time frame: Throughout hospital stay, or an average of 1 week.
Levels of Blood Oxygen Saturation
Time frame: Throughout stay in the recovery unit, or an average of 1-2 days.
Length of Stay in the Recovery Unit
Time frame: Throughout stay in the recovery unit, or an average of 1-2 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24346178American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):268-86. doi: 10.1097/ALN.0000000000000053. No abstract available.
- Background: PubMed 24756518Aisen PS. Serum brain-derived neurotrophic factor and the risk for dementia. JAMA. 2014 Apr 23-30;311(16):1684-5. doi: 10.1001/jama.2014.3120. No abstract available.
- Background: PubMed 23518041Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, Naseem J, Asif A, Bawaadam H. Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013 Mar 22;10:13. doi: 10.1186/1476-9255-10-13. eCollection 2013.
- Background: PubMed 22337162Flink BJ, Rivelli SK, Cox EA, White WD, Falcone G, Vail TP, Young CC, Bolognesi MP, Krystal AD, Trzepacz PT, Moon RE, Kwatra MM. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology. 2012 Apr;116(4):788-96. doi: 10.1097/ALN.0b013e31824b94fc.
- Background: PubMed 21106342Grandi C, Tomasi CD, Fernandes K, Stertz L, Kapczinski F, Quevedo J, Dal-Pizzol F, Ritter C. Brain-derived neurotrophic factor and neuron-specific enolase, but not S100beta, levels are associated to the occurrence of delirium in intensive care unit patients. J Crit Care. 2011 Apr;26(2):133-7. doi: 10.1016/j.jcrc.2010.10.006. Epub 2010 Nov 23.
- Background: PubMed 22670023Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest. 2012 Jun;141(6):1601-1610. doi: 10.1378/chest.11-2214.
- Background: PubMed 23541562Lim DC, Pack AI. Obstructive sleep apnea and cognitive impairment: addressing the blood-brain barrier. Sleep Med Rev. 2014 Feb;18(1):35-48. doi: 10.1016/j.smrv.2012.12.003. Epub 2013 Mar 28.
- Background: PubMed 15032653Nakajima K, Kohsaka S. Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord. 2004 Mar;4(1):65-84. doi: 10.2174/1568006043481284.
- Background: PubMed 24127144Nadeem R, Molnar J, Madbouly EM, Nida M, Aggarwal S, Sajid H, Naseem J, Loomba R. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med. 2013 Oct 15;9(10):1003-12. doi: 10.5664/jcsm.3070.
- Background: PubMed 11205147Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl. 2000;(60):277-90. doi: 10.1007/978-3-7091-6301-6_19.
- Background: PubMed 20865453Panaree B, Chantana M, Wasana S, Chairat N. Effects of obstructive sleep apnea on serum brain-derived neurotrophic factor protein, cortisol, and lipid levels. Sleep Breath. 2011 Dec;15(4):649-56. doi: 10.1007/s11325-010-0415-7. Epub 2010 Sep 24.
- Background: PubMed 23950649Yang Q, Wang Y, Feng J, Cao J, Chen B. Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia. Neuropsychiatr Dis Treat. 2013;9:1077-86. doi: 10.2147/NDT.S49868. Epub 2013 Aug 5.
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Apnea, Sleep Disorders
Not yet recruitingPhase 2
Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use.
Sleep-disordered Breathing, Chronic Opioid Use
Recruiting
Nightly Wearable Monitoring During Home-Based Submental Electrical Stimulation for Obstructive Sleep Apnea
Obstructive Sleep Apnea
RecruitingPhase 1/2
DRonabinol Treatment of OSA
Obstructive Sleep Apnea
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kethy M Jules-Elysee, MD principal investigator
Hospital for Special Surgery, New York
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lumbar Puncture (Standard-of-Care) in people with Obstructive Sleep Apnea, run by Hospital for Special Surgery, New York at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum IL-6 (Interleukin 6) Levels (time frame: Intraoperatively - Pre-Incision). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02325687, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.